Roles of p75NTR in Maintaining Brain Hemostasis and the Implications for p75NTR-targeted Therapies

The p75 neurotrophin receptor (p75NTR) is a single membrane-spanning receptor in the tumor necrosis factor (TNF) death domain containing receptor family. p75NTR has multiple faces of biological or pathogenic functions by partnering with the three major neurotrophin receptors, including tropomyosin receptor kinase (Trk), sortilin and Nogo receptors. By partnering with different co-receptors, p75NTR regulates the binding of mature or pro-neurotrophins and activation of different signaling pathways, resulting in outcomes ranging from growth and survival to cell death or apoptosis. In this review, we summarized the role of p75NTR in maintaining the hemostasis of the brain, and briefly introduced its participation in the pathogenesis of several neurodegenerative diseases. The complexity of p75NTR enables it to be a potent therapeutic target of many diseases by modulating functions of the receptor.